Behavioral interactions between opiate and antiepileptic drugs in the mouse

Morphine and related opioid compounds are known to possess proconvulsant activity based upon both electroencephalographic and behavioral criteria. The present authors previously suggested that opiate-related seizures were behaviorally inhibitory, and this was further investigated in the present study. The effects of pretreatment with three pharmacologically distinct compounds (sodium valproic acid, trimethadione, taurine) upon normal behavioral activation to systemic morphine were examined in the mouse. Morphine consistently increased activity levels in comparison with vehicle. Each of the three experimental compounds itself was behaviorally inhibitory; nonetheless both sodium valproate and trimethadione facilitated behavioral responses to morphine. The effects of the same drugs upon activation produced by central administration of a long-lasting enkephalin analog (-ala2-leu-enkephalinamide) were investigated, with similar results. These findings confirm a behavioral interaction between opiate and anticonvulsant drugs, although it may be selective for certain classes of anticonvulsant compounds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24414/1/0000684.pd

Conductivity sum rule, implication for in-plane dynamics and c-axis response

Recently observed $c$-axis optical sum rule violations indicate non-Fermi liquid in-plane behavior. For coherent $c$-axis coupling, the observed flat, nearly frequency independent $c$-axis conductivity $\sigma_{1}(\omega)$ implies a large in-plane scattering rate $\Gamma$ around $(0,\pi)$ and therefore any pseudogap that might form at low frequency in the normal state will be smeared. On the other hand incoherent $c$-axis coupling places no restriction on the value of $\Gamma$ and gives a more consistent picture of the observed sum rule violation which, we find in some cases, can be less than half.Comment: 3 figures. To appear in PR

A Search for Ultra-High Energy Counterparts to Gamma-Ray Bursts

A small air shower array operating over many years has been used to search for ultra-high energy (UHE) gamma radiation ($\geq 50$ TeV) associated with gamma-ray bursts (GRBs) detected by the BATSE instrument on the Compton Gamma-Ray Observatory (CGRO). Upper limits for a one minute interval after each burst are presented for seven GRBs located with zenith angles $\theta < 20^{\circ}$. A $4.3\sigma$ excess over background was observed between 10 and 20 minutes following the onset of a GRB on 11 May 1991. The confidence level that this is due to a real effect and not a background fluctuation is 99.8\%. If this effect is real then cosmological models are excluded for this burst because of absorption of UHE gamma rays by the intergalactic radiation fields.Comment: 4 pages LaTeX with one postscript figure. This version does not use kluwer.sty and will allow automatic postscript generatio

Stress induced grooming in the rat -- An endorphin mediated syndrome

Exposure of adult male Sprague--Dawley rats to a non-traumatic noise-light stress procedure subsequently increased grooming behavior in a novel environment. The grooming syndrome was marginally facilitated by adrenalectomy and by hypophysectomy. Opiate blockade by naltrexone returned grooming to basal levels. This suggests that stress induced grooming is not dependent upon pituitary-adrenal integrity for its expression, although it may be modulated by the latter. On the other hand this form of grooming may depend upon an endogenous opiate system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23542/1/0000501.pd

Sequential cavity method for computing free energy and surface pressure

We propose a new method for the problems of computing free energy and surface pressure for various statistical mechanics models on a lattice $\Z^d$. Our method is based on representing the free energy and surface pressure in terms of certain marginal probabilities in a suitably modified sublattice of $\Z^d$. Then recent deterministic algorithms for computing marginal probabilities are used to obtain numerical estimates of the quantities of interest. The method works under the assumption of Strong Spatial Mixing (SSP), which is a form of a correlation decay. We illustrate our method for the hard-core and monomer-dimer models, and improve several earlier estimates. For example we show that the exponent of the monomer-dimer coverings of $\Z^3$ belongs to the interval $[0.78595,0.78599]$, improving best previously known estimate of (approximately) $[0.7850,0.7862]$ obtained in \cite{FriedlandPeled},\cite{FriedlandKropLundowMarkstrom}. Moreover, we show that given a target additive error $\epsilon>0$, the computational effort of our method for these two models is $(1/\epsilon)^{O(1)}$ \emph{both} for free energy and surface pressure. In contrast, prior methods, such as transfer matrix method, require $\exp\big((1/\epsilon)^{O(1)}\big)$ computation effort.Comment: 33 pages, 4 figure

On the complexity of strongly connected components in directed hypergraphs

We study the complexity of some algorithmic problems on directed hypergraphs and their strongly connected components (SCCs). The main contribution is an almost linear time algorithm computing the terminal strongly connected components (i.e. SCCs which do not reach any components but themselves). "Almost linear" here means that the complexity of the algorithm is linear in the size of the hypergraph up to a factor alpha(n), where alpha is the inverse of Ackermann function, and n is the number of vertices. Our motivation to study this problem arises from a recent application of directed hypergraphs to computational tropical geometry. We also discuss the problem of computing all SCCs. We establish a superlinear lower bound on the size of the transitive reduction of the reachability relation in directed hypergraphs, showing that it is combinatorially more complex than in directed graphs. Besides, we prove a linear time reduction from the well-studied problem of finding all minimal sets among a given family to the problem of computing the SCCs. Only subquadratic time algorithms are known for the former problem. These results strongly suggest that the problem of computing the SCCs is harder in directed hypergraphs than in directed graphs.Comment: v1: 32 pages, 7 figures; v2: revised version, 34 pages, 7 figure

Exact results for hydrogen recombination on dust grain surfaces

The recombination of hydrogen in the interstellar medium, taking place on surfaces of microscopic dust grains, is an essential process in the evolution of chemical complexity in interstellar clouds. The H_2 formation process has been studied theoretically, and in recent years also by laboratory experiments. The experimental results were analyzed using a rate equation model. The parameters of the surface, that are relevant to H_2 formation, were obtained and used in order to calculate the recombination rate under interstellar conditions. However, it turned out that due to the microscopic size of the dust grains and the low density of H atoms, the rate equations may not always apply. A master equation approach that provides a good description of the H_2 formation process was proposed. It takes into account both the discrete nature of the H atoms and the fluctuations in the number of atoms on a grain. In this paper we present a comprehensive analysis of the H_2 formation process, under steady state conditions, using an exact solution of the master equation. This solution provides an exact result for the hydrogen recombination rate and its dependence on the flux, the surface temperature and the grain size. The results are compared with those obtained from the rate equations. The relevant length scales in the problem are identified and the parameter space is divided into two domains. One domain, characterized by first order kinetics, exhibits high efficiency of H_2 formation. In the other domain, characterized by second order kinetics, the efficiency of H_2 formation is low. In each of these domains we identify the range of parameters in which, the rate equations do not account correctly for the recombination rate. and the master equation is needed.Comment: 23 pages + 8 figure

Dopaminergic involvement in attention a novel animal model

1. 1. Adult male outbred albino mice were acutely injected with either of two dopamine (DA) agonists; Apomorphine, a receptor agonist, or Amantadine, a DA releasing agent.2. 2. Both drugs produced dose-related alterations in initial Y-maze behavior, consisting of significantly increased proportions of 2-arm entries.3. 3. This behavior has previously been shown to reflect an abnormal attentional process.4. 4. Thus DA activation may cause sensory perseveration.5. 5. The implications of this finding for DA theories of psychopathology is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24570/1/0000852.pd

Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes

Background and objectives In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. Design, setting, participants, & measurements The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. Results There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). Conclusions In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events